The Test

How is it used?

Syphilis tests are used to screen for and/or diagnose infection with Treponema pallidum, the bacteria that cause syphilis. Several different types of tests are available. Antibody tests are most commonly used.

Antibody tests (serology)—these tests detect antibodies in the blood and sometimes in the cerebrospinal fluid (CSF). Two general types are available for syphilis testing, nontreponemal and treponemal (derived from the name of the bacterium). Either type may be used for syphilis screening but must be followed by a second test that uses a different method to confirm a positive result and to diagnose active syphilis:

Nontreponemal antibody tests--these tests are called "nontreponemal" because they detect antibodies that are not specifically directed against the Treponema pallidum bacteria. These antibodies are produced by the body when an individual has syphilis but may also be produced in several other conditions. The tests are highly sensitive but, since they are non-specific, false-positive results can be caused by, for example, IV drug use, pregnancy, Lyme disease, certain types of pneumonia, malaria, tuberculosis, or certain autoimmune disorders including lupus. A positive screening result must be confirmed with a more specific (treponemal) test. Nontreponemal tests include:

RPR (Rapid Plasma Reagin)--in addition to screening, this test is useful in monitoring treatment for syphilis. For this purpose, the level (titer) of antibody is measured. It may also be used to confirm the presence of an active infection when an initial test for treponemal antibodies is positive (see below).

VDRL (Venereal Disease Research Laboratory)--in addition to blood, this test is primarily performed on CSF to help diagnose neurosyphilis.

Treponemal antibody tests--these blood tests detect antibodies that specifically target T. pallidum. They are highly specific for syphilis, meaning other conditions are unlikely to cause a positive result. However, once a person is infected and these antibodies develop, they remain in the blood for life. By comparison, nontreponemal antibodies typically disappear in an adequately treated person after about 3 years. Therefore, a positive treponemal screening result must be followed by a nontreponemal test (such as RPR) to differentiate between an active infection (or reinfection) and one that occurred in the past and was successfully treated. Treponemal antibody tests include:

FTA-ABS (Fluorescent treponemal antibody absorption)--this test is useful after the first 3-4 weeks following exposure. In addition to blood testing, it can be used to measure antibodies to T. pallidum in the CSF to help diagnose neurosyphilis.

TP-PA (T. pallidum particle agglutination assay)--this test is sometimes performed instead of FTA-ABS because it is more specific and there are fewer false positives.

MHA-TP (Microhemagglutination assay)--another confirmatory method; this test is used much less commonly now.

Immunoassays (AIA)--in more recent years, several automated tests have been developed, making them convenient for screening purposes.

Direct detection of bacteria—these tests are less commonly performed:

Darkfield microscopy--this method may be used in the early stages of syphilis when a suspected syphilis sore (chancre) is present. It involves obtaining a scraping of the sore, placing it on a slide, and examining it with a special instrument called a dark-field microscope.

Molecular testing (polymerase chain reaction, PCR)--this test detects genetic material from the bacteria in the sample from the sore, in blood, or in CSF.

Syphilis Tests

The following table summarizes the stages of syphilis and types of tests that may be used:

Stages of disease:

Exposure to bacteria

Chancre, "Primary syphilis"

Skin eruptions, "Secondary syphilis"

Neurological disease, "Tertiary syphilis"

The time after exposure that these stages may occur if the person is not treated

Day 1

10-90 days

6 weeks to 6 months

10-30 years

Description

Transmission of syphilis occurs during vaginal, anal, or oral sex. Pregnant women with the disease can transmit it to unborn child. First-time infection provides no immunity; re-infection can occur if exposed a second time.

Appearance of a single sore, though there may be multiple sores at the location(s) where the bacteria entered the body. The sore is usually firm, round, and painless and can easily go unnoticed. It lasts 3-6 weeks and heals regardless of whether or not the person is treated.

Rash on one or more areas of the body can appear from the time when the primary sore is healing to several weeks after the sore has healed. Rash usually does not itch and is unusual in that it can occur on palms of hands and soles of feet.

Nontreponemal Antibody Tests: VDRL and RPR. Used to screen or confirm a positive treponemal antibody test; used to guide treatment.

Highly sensitive; positive screening results must be confirmed with treponemal antibody test as it may be positive in other conditions. Nontreponemal antibodies typically disappear in an adequately treated person after about 3 years.

Highly specific; positive screening results must be followed by nontreponemal antibody test to differentiate between active and past infection. These antibodies remain positive for life even after treatment.

Same as primary stage

The CSF FTA-ABS is less specific than VDRL, but the test is highly sensitive; can be used to exclude neurosyphilis.

Direct detection tests (much less common):

Microscopic Exam, Darkfield Exam: Sample from chancre is placed on a slide, examined with a special microscope.

What does the test result mean?

Care must be taken when interpreting results from tests for syphilis.

Antibody tests:

A negative blood test means that it is likely that no infection is present. However, a negative screening test means only that there is no evidence of disease at the time of the test. Antibodies may not be detected for up to several weeks after exposure to the bacteria. If a person knows he or she has been exposed, or if suspicion of infection remains high, then repeat testing at a later date may be required. It is also important for those who are at increased risk of syphilis infection to have screening tests performed regularly to check for possible infection.

A positive RPR or VDRL screen must be followed by a specific treponemal antibody test (e.g., FTA-ABS, TP-PA):

A positive result on the second method confirms the screening result and the affected person is diagnosed with syphilis.

A negative result on the treponemal test may mean that the initial RPR or VDRL test was falsely positive. Further testing and investigation may be done to determine the cause of the false positive.

Alternatively, a doctor or laboratory will use a treponemal antibody test as an initial test. A positive result indicates the presence of syphilis antibodies in the blood, but since treponemal antibodies remain positive even after an infection has been treated, it does not indicate whether the person has a current infection or was infected in the past. Conversely, nontreponemal antibodies as detected with an RPR typically disappear in an adequately treated person after about 3 years. Thus, if an initial treponemal test is positive, an RPR can be performed to differentiate between an active or past infection. In this case, a positive RPR would confirm that the person has been exposed to syphilis and, if not treated previously, has an active infection or, if treatment had occurred more than 3 years ago, possible re-infection.

For monitoring treatment and/or determining if treatment was successful, the results of one or more RPR titers may be evaluated. Syphilis antibodies should be lower following treatment. For example, if the RPR was initially reported as 1:256, a value of 1:16 after treatment would indicate a lower level of antibody. If the titer remains the same or rises, the affected person may have a persistent infection or was reinfected. Results may also be expressed as dilutions (e.g., 1/16) or converted to a whole number (e.g., 16 dils).

CSF tests:

Results of syphilis tests performed on CSF samples, usually when someone has late or latent stages of the disease with suspected brain involvement (neurosyphilis), are often interpreted in conjunction with a blood test as well as the affected person's signs, symptoms, and medical history.

A positive VDRL or FTA-ABS result on a sample of CSF indicates likely infection of the central nervous system. A negative result, especially on an FTA-ABS, may help to rule out infection of the central nervous system.

Direct detection:

If a scraping from a suspected syphilis sore reveals presence of the syphilis bacteria (a positive test on either darkfield microscopy or PCR), the person being tested has an infection that requires treatment with a course of antibiotics, preferably penicillin.

A negative result from a scraping may mean that there is no syphilis infection present and symptoms are due to another cause or that there were insufficient bacteria present in the sample to be detected.

After successful treatment, nontreponemal antibodies disappear over time; treponemal antibodies are present in the blood for life.

Is there anything else I should know?

The different tests available to screen for and diagnose syphilis vary in their accuracy depending on the stage of disease.

If you are sexually active, you should consult your doctor about any suspicious rash or sore in the genital area; there are many other sexually transmitted diseases besides syphilis. If you are infected, tell your sexual partner(s) to get tested and treated.

The risk of contracting other STDs increases if you have syphilis sores. You are 2 to 5 times more likely to be infected with HIV, if exposed, when syphilis sores are present, according to the CDC. If you have such chancres and have not been diagnosed with HIV, you should be tested for HIV.

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This article was last reviewed on April 29, 2013. | This article was last modified on February 24, 2015.

The review date indicates when the article was last reviewed from beginning to end to ensure that it reflects the most current science. A review may not require any modifications to the article, so the two dates may not always agree.

The modified date indicates that one or more changes were made to the article. Such changes may or may not result from a full review of the article, so the two dates may not always agree.